ArticleThe Journal of biological chemistry2016
The Tumor-suppressive Small GTPase DiRas1 Binds the Noncanonical Guanine Nucleotide Exchange Factor SmgGDS and Antagonizes SmgGDS Interactions with Oncogenic Small GTPases.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- DIRAS1 Drives Oxaliplatin Resistance in Colorectal Cancer via PHB1-Mediated Mitochondrial Homeostasis.Biology · 2025Article
- M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells.Cancer biology & therapy · 2024Article
- Article
- A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival.Frontiers in genetics · 2022Article
- DIRAS2 Is a Prognostic Biomarker and Linked With Immune Infiltrates in Melanoma.Frontiers in oncology · 2022Article
- Diverse Ras-related GTPase DIRAS2, downregulated by PSMD2 in a proteasome-mediated way, inhibits colorectal cancer proliferation by blocking NF-κB signaling.International journal of biological sciences · 2022Article
- Frequent Epigenetic Inactivation of DIRAS-1 and DIRAS-2 Contributes to Chemo-Resistance in Gliomas.Cancers · 2021Article
- SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.Frontiers in molecular biosciences · 2021Review
- LINC00261 Inhibits Esophageal Cancer Radioresistance by Down-Regulating microRNA-552-3p and Promoting DIRAS1.Cancer management and research · 2021Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases.The Journal of biological chemistry · 2019Article
- GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated RhoA complex and its implication for a chaperone mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- RNAa and Vector-Mediated Overexpression of DIRAS1 Suppresses Tumor Growth and Migration in Renal Cell Carcinoma.Molecular therapy. Nucleic acids · 2018Article
- Sodium butyrate induces cell death by autophagy and reactivates a tumor suppressor gene DIRAS1 in renal cell carcinoma cell line UOK146.In vitro cellular & developmental biology. Animal · 2018Article
- RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells.Autophagy · 2018Article
- Structure-based analysis of the guanine nucleotide exchange factor SmgGDS reveals armadillo-repeat motifs and key regions for activity and GTPase binding.The Journal of biological chemistry · 2017Article
- Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Methylation ofClinical epigenetics · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
The small GTPase DiRas1 has tumor-suppressive activities, unlike the oncogenic properties more common to small GTPases such as K-Ras and RhoA. Although DiRas1 has been found to be a tumor suppressor in gliomas and esophageal squamous cell carcinomas, the mechanisms by which it inhibits malignant phenotypes have not been fully determined. In this study, we demonstrate that DiRas1 binds to SmgGDS, a protein that promotes the activation of several oncogenic GTPases. In silico docking studies predict that DiRas1 binds to SmgGDS in a manner similar to other small GTPases. SmgGDS is a guanine nucleotide exchange factor for RhoA, but we report here that SmgGDS does not mediate GDP/GTP exchange on DiRas1. Intriguingly, DiRas1 acts similarly to a dominant-negative small GTPase, binding to SmgGDS and inhibiting SmgGDS binding to other small GTPases, including K-Ras4B, RhoA, and Rap1A. DiRas1 is expressed in normal breast tissue, but its expression is decreased in most breast cancers, similar to its family member DiRas3 (ARHI). DiRas1 inhibits RhoA- and SmgGDS-mediated NF-κB transcriptional activity in HEK293T cells. We also report that DiRas1 suppresses basal NF-κB activation in breast cancer and glioblastoma cell lines. Taken together, our data support a model in which DiRas1 expression inhibits malignant features of cancers in part by nonproductively binding to SmgGDS and inhibiting the binding of other small GTPases to SmgGDS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.